Alimentary Pharmacology and Therapeutics
Invited Editorials Editorial: would an aspirin a day keep NAFLD and its complications away? M. J. Armstrong & I. A. Rowe NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK. E-mail: [email protected] doi:10.1111/apt.12998
Non-alcoholic fatty liver disease (NAFLD) is associated with progressive liver disease to cirrhosis in a small proportion of patients, with the majority of deaths attributed to cardiovascular disease. Lifestyle modifications are the cornerstone of the management of individuals with NAFLD. In designing the ideal pharmacological option, one would aim for safe and cost-effective prevention of progressive liver disease, and arguably more importantly a reduction in the associated cardiovascular morbidity and mortality.1 Shen et al. have taken the first early steps to understand whether aspirin could be a feasible beneficial option in NAFLD.2 The authors utilised the extensively studied US NHANES III cohort to suggest that regular aspirin use (defined as >159 per month) is associated with a lower prevalence of ultrasound-defined NAFLD in men. As acknowledged by the authors the cross-sectional design prohibited any analysis of the causal effect of aspirin on the prevalence reduction in NAFLD or indeed the relevance of the described gender disparity. The strength of the study is that a large number of the general population (>11 000) underwent a thorough work-up, including ultrasound, serological testing and standardised questionnaires to define NAFLD; thereby allowing adjustment of potential demographical and metabolic confounders.2 Although the well-recognised limitations of self-reported data and ultrasound as a diagnostic tool are acceptable within the confines of population-based studies, they increase the risk of mis-classifying those with and without NAFLD. This may partly explain the surprising higher percentage of aspirin usage in the controls than the NAFLD population (8.9% vs.
7.7%), who have significantly more cardiovascular risk factors.2 Throughout the NHANES III studies3, 4 those participants with mild fatty liver on ultrasound have been categorised into the control arm. In the knowledge that liver fat content is decreased towards the more advanced stages of NAFLD, and in particular in cirrhosis,5 this increases the risk of underestimating the inverse association between aspirin usage and NAFLD. This is exemplified by the observation that the association was stronger (to an unreported degree) when those with mild fatty liver on ultrasound were re-categorised into the NAFLD group.2 The strong association between NAFLD and cardiovascular risk1 argues that future studies of aspirin should primarily focus on the incidence of major cardiovascular end-points, rather than liver disease progression per se. However, the feasibility of such a study would be limited by the long study duration and large sample size, which would be required to determine the benefits and harms of this approach. Therefore, evaluation of the efficacy of aspirin usage in NAFLD is likely to be drawn from observational and retrospective studies only.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 2014; 59: 1174–97. 2. Shen H, Shahzad G, Jawairia M, et al. Association between aspirin use and the prevalence of nonalcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey. Aliment Pharmacol Ther 2014; 40: 1066–73. 3. Lazo M, Hernaez R, Bonekamp S, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011; 343: d6891. 4. Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012; 10: 646–50. 5. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745–50.
AP&T invited editorial columns are restricted to discussing papers that have been published in the journal. An editorial must have a maximum of 300 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.
ª 2014 John Wiley & Sons Ltd
145
Copyright of Alimentary Pharmacology & Therapeutics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Invited Editorials Editorial: would an aspirin a day keep NAFLD and its complications away? M. J. Armstrong & I. A. Rowe NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK. E-mail: [email protected] doi:10.1111/apt.12998
Non-alcoholic fatty liver disease (NAFLD) is associated with progressive liver disease to cirrhosis in a small proportion of patients, with the majority of deaths attributed to cardiovascular disease. Lifestyle modifications are the cornerstone of the management of individuals with NAFLD. In designing the ideal pharmacological option, one would aim for safe and cost-effective prevention of progressive liver disease, and arguably more importantly a reduction in the associated cardiovascular morbidity and mortality.1 Shen et al. have taken the first early steps to understand whether aspirin could be a feasible beneficial option in NAFLD.2 The authors utilised the extensively studied US NHANES III cohort to suggest that regular aspirin use (defined as >159 per month) is associated with a lower prevalence of ultrasound-defined NAFLD in men. As acknowledged by the authors the cross-sectional design prohibited any analysis of the causal effect of aspirin on the prevalence reduction in NAFLD or indeed the relevance of the described gender disparity. The strength of the study is that a large number of the general population (>11 000) underwent a thorough work-up, including ultrasound, serological testing and standardised questionnaires to define NAFLD; thereby allowing adjustment of potential demographical and metabolic confounders.2 Although the well-recognised limitations of self-reported data and ultrasound as a diagnostic tool are acceptable within the confines of population-based studies, they increase the risk of mis-classifying those with and without NAFLD. This may partly explain the surprising higher percentage of aspirin usage in the controls than the NAFLD population (8.9% vs.
7.7%), who have significantly more cardiovascular risk factors.2 Throughout the NHANES III studies3, 4 those participants with mild fatty liver on ultrasound have been categorised into the control arm. In the knowledge that liver fat content is decreased towards the more advanced stages of NAFLD, and in particular in cirrhosis,5 this increases the risk of underestimating the inverse association between aspirin usage and NAFLD. This is exemplified by the observation that the association was stronger (to an unreported degree) when those with mild fatty liver on ultrasound were re-categorised into the NAFLD group.2 The strong association between NAFLD and cardiovascular risk1 argues that future studies of aspirin should primarily focus on the incidence of major cardiovascular end-points, rather than liver disease progression per se. However, the feasibility of such a study would be limited by the long study duration and large sample size, which would be required to determine the benefits and harms of this approach. Therefore, evaluation of the efficacy of aspirin usage in NAFLD is likely to be drawn from observational and retrospective studies only.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 2014; 59: 1174–97. 2. Shen H, Shahzad G, Jawairia M, et al. Association between aspirin use and the prevalence of nonalcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey. Aliment Pharmacol Ther 2014; 40: 1066–73. 3. Lazo M, Hernaez R, Bonekamp S, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011; 343: d6891. 4. Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012; 10: 646–50. 5. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745–50.
AP&T invited editorial columns are restricted to discussing papers that have been published in the journal. An editorial must have a maximum of 300 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.
ª 2014 John Wiley & Sons Ltd
145
Copyright of Alimentary Pharmacology & Therapeutics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
